{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T20:49:26Z","timestamp":1791492566860,"version":"4.3.4"},"reference-count":34,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2026,8,30]],"date-time":"2026-08-30T00:00:00Z","timestamp":1788048000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,9,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Atrial and ventricular ectopy are frequently encountered during ambulatory monitoring in asymptomatic adults; however, their independent long-term prognostic significance in low-risk populations without structural heart disease remains a subject of ongoing clinical debate.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>To identify the distinct clinical and physiological determinants of atrial ectopic burden (AEB) and ventricular ectopic burden (VEB) and to evaluate their independent long-term associations with major adverse cardiovascular events (MACE) in a primary prevention cohort.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>We evaluated 931 asymptomatic individuals (mean age 52 \u00b1 7 years; 13% female) without structural heart disease who completed a baseline 24-h Holter recording. High AEB and VEB were defined using cohort-specific medians and\/or the presence of ambulatory arrhythmic complexity. Complete longitudinal tracking for MACE (composite of acute coronary syndrome, cerebrovascular accident, new-onset heart failure, or cardiovascular mortality) was available for 840 participants over a median follow-up of 8 years (IQR 5\u201311 years). To evaluate the robustness of the atrial findings, a prespecified sensitivity analysis was performed by excluding patients with baseline atrial fibrillation. Over the follow-up period, the primary MACE endpoint occurred in 149 (18%) participants. In multivariable logistic regression models, high AEB was independently driven by older age (OR 1.09, 95% CI 1.06\u20131.12; P &amp;lt; 0.001), male sex (OR 1.60, 95% CI 1.02\u20132.52; P = 0.042), reduced estimated glomerular filtration rate (eGFR) (OR 0.98, 95% CI 0.97\u20130.99; P = 0.049), and low cardiorespiratory fitness (OR 1.38, 95% CI 1.01\u20131.92; P = 0.049). Conversely, high VEB was independently associated only with older age (OR 1.04, 95% CI 1.02\u20131.07; P &amp;lt; 0.001) and reduced eGFR (OR 0.98, 95% CI 0.977\u20130.99; P = 0.034). In fully adjusted multivariable Cox proportional hazards models, high VEB remained a robust independent predictor of MACE, conferring a three-fold increase in risk (HR 3.06, 95% CI 2.06\u20134.56; P &amp;lt; 0.001). In tertile-based analyses of pure ectopic burden, increasing VEB demonstrated a robust graded association with MACE after adjustment for age, sex, beta-blocker use, and antiarrhythmic drug therapy (HR per tertile increase 2.02, 95% CI 1.60\u20132.53; P &amp;lt; 0.001), whereas AEB showed only a borderline association that did not reach statistical significance (HR per tertile increase 1.21, 95% CI 0.98\u20131.50; P = 0.076).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>In asymptomatic adults without structural heart disease, the clinical determinants and long-term prognostic trajectories of ectopy exhibit a profound chamber-specific divergence. Ventricular ectopic burden stands out as a powerful, independent marker of intrinsic electrical vulnerability and long-term cardiovascular risk. Meanwhile, atrial ectopy is highly sensitive to systemic physiological fitness and carries a weaker prognostic signal that attenuates completely upon multivariate clinical and medication adjustment.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/ehjopen\/oeag133","type":"journal-article","created":{"date-parts":[[2026,8,30]],"date-time":"2026-08-30T06:01:40Z","timestamp":1788069700000},"source":"Crossref","is-referenced-by-count":0,"title":["Determinants and prognostic value of atrial and ventricular ectopic burden in adults without structural heart disease"],"prefix":"10.1093","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-9095-6619","authenticated-orcid":false,"given":"Amit","family":"Moses","sequence":"first","affiliation":[{"name":"Leviev Heart Center, Sheba Medical Center, Affiliated with Sackler School of Medicine, Tel Aviv University , Sheba Road 2, Ramat Gan, Tel Aviv 5265601, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-9263-6389","authenticated-orcid":false,"given":"Rotem","family":"Givoli Vilensky","sequence":"additional","affiliation":[{"name":"Internal Medicine Ward C, Sheba Medical Center, Affiliated with Sackler School of Medicine, Tel Aviv University , Sheba Road 2, Ramat Gan, Tel Aviv 5265601, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noam","family":"Makmal","sequence":"additional","affiliation":[{"name":"Leviev Heart Center, Sheba Medical Center, Affiliated with Sackler School of Medicine, Tel Aviv University , Sheba Road 2, Ramat Gan, Tel Aviv 5265601, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-3538-2889","authenticated-orcid":false,"given":"Kobi","family":"Faierstein","sequence":"additional","affiliation":[{"name":"Leviev Heart Center, Sheba Medical Center, Affiliated with Sackler School of Medicine, Tel Aviv University , Sheba Road 2, Ramat Gan, Tel Aviv 5265601, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elad","family":"Maor","sequence":"additional","affiliation":[{"name":"Leviev Heart Center, Sheba Medical Center, Affiliated with Sackler School of Medicine, Tel Aviv University , Sheba Road 2, Ramat Gan, Tel Aviv 5265601, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9268-4766","authenticated-orcid":false,"given":"Roy","family":"Beinart","sequence":"additional","affiliation":[{"name":"Leviev Heart Center, Sheba Medical Center, Affiliated with Sackler School of Medicine, Tel Aviv University , Sheba Road 2, Ramat Gan, Tel Aviv 5265601, Israel"},{"name":"Davidai Arrhythmia Center, Sheba Medical Center, Affiliated with Sackler School of Medicine, Tel Aviv University , Sheba Road 2, Ramat Gan, Tel Aviv 5265601, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4295-6679","authenticated-orcid":false,"given":"Avi","family":"Sabbag","sequence":"additional","affiliation":[{"name":"Leviev Heart Center, Sheba Medical Center, Affiliated with Sackler School of Medicine, Tel Aviv University , Sheba Road 2, Ramat Gan, Tel Aviv 5265601, Israel"},{"name":"Davidai Arrhythmia Center, Sheba Medical Center, Affiliated with Sackler School of Medicine, Tel Aviv University , Sheba Road 2, Ramat Gan, Tel Aviv 5265601, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,8,30]]},"reference":[{"key":"2026100816023369300_oeag133-B1","doi-asserted-by":"crossref","first-page":"1852","DOI":"10.1016\/j.amjcard.2015.09.025","article-title":"Frequent atrial premature complexes and their association with risk of atrial fibrillation","volume":"116","author":"Acharya","year":"2015","journal-title":"Am J Cardiol"},{"key":"2026100816023369300_oeag133-B2","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1093\/cvr\/cvac054","article-title":"Frequent premature atrial contractions as a signalling marker of atrial cardiomyopathy, incident atrial fibrillation, and stroke","volume":"119","author":"Farinha","year":"2023","journal-title":"Cardiovasc Res"},{"key":"2026100816023369300_oeag133-B3","doi-asserted-by":"crossref","DOI":"10.3389\/fphys.2022.971691","article-title":"Premature atrial contractions: a predictor of atrial fibrillation and a relevant marker of atrial cardiomyopathy","volume":"13","author":"Guichard","year":"2022","journal-title":"Front Physiol"},{"key":"2026100816023369300_oeag133-B4","doi-asserted-by":"crossref","first-page":"e91","DOI":"10.1016\/j.jacc.2017.10.054","article-title":"2017 AHA\/ACC\/HRS guideline for management of patients with ventricular arrhythmias and the prevention of sudden cardiac death","volume":"72","author":"Al-Khatib","year":"2018","journal-title":"J Am Coll Cardiol"},{"key":"2026100816023369300_oeag133-B5","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1002\/joa3.12338","article-title":"European Heart Rhythm Association (EHRA)\/Heart Rhythm Society (HRS)\/Asia Pacific Heart Rhythm Society (APHRS)\/Latin American Heart Rhythm Society (LAHRS) expert consensus on risk assessment in cardiac arrhythmias: use the right tool for the right outcome, in the right population","volume":"36","author":"Nielsen","year":"2020","journal-title":"J Arrhythmia"},{"key":"2026100816023369300_oeag133-B6","doi-asserted-by":"crossref","DOI":"10.1161\/JAHA.117.006028","article-title":"Ectopy on a single 12-lead ECG, incident cardiac myopathy, and death in the community","volume":"6","author":"Nguyen","year":"2017","journal-title":"J Am Heart Assoc"},{"key":"2026100816023369300_oeag133-B7","doi-asserted-by":"crossref","first-page":"e5","DOI":"10.1016\/j.hrthm.2014.11.011","article-title":"Progress toward the prevention and treatment of atrial fibrillation: a summary of the Heart Rhythm Society Research Forum on the Treatment and Prevention of Atrial Fibrillation, Washington, DC, December 9\u201310, 2013","volume":"12","author":"Van Wagoner","year":"2015","journal-title":"Heart Rhythm"},{"key":"2026100816023369300_oeag133-B8","doi-asserted-by":"crossref","first-page":"1219","DOI":"10.1111\/ene.13970","article-title":"Association between excessive supraventricular ectopy and subclinical cerebrovascular disease: a population-based study","volume":"26","author":"Hisamatsu","year":"2019","journal-title":"Eur J Neurol"},{"key":"2026100816023369300_oeag133-B9","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/j.amjcard.2021.04.020","article-title":"Prognostic implications of supraventricular arrhythmias","volume":"151","author":"Hygrell","year":"2021","journal-title":"Am J Cardiol"},{"key":"2026100816023369300_oeag133-B10","doi-asserted-by":"crossref","first-page":"1732","DOI":"10.1136\/heartjnl-2020-316925","article-title":"Establishing reference ranges for ambulatory electrocardiography parameters: meta-analysis","volume":"106","author":"Williams","year":"2020","journal-title":"Heart"},{"key":"2026100816023369300_oeag133-B11","doi-asserted-by":"crossref","DOI":"10.1161\/JAHA.120.018093","article-title":"Associations of left atrial function and structure with supraventricular ectopy: the multi-ethnic study of atherosclerosis","volume":"10","author":"Heckbert","year":"2021","journal-title":"J Am Heart Assoc"},{"key":"2026100816023369300_oeag133-B12","doi-asserted-by":"crossref","first-page":"1373","DOI":"10.1016\/j.amjcard.2013.06.028","article-title":"Effect of mildly attenuated heart rate response during treadmill exercise testing on cardiovascular outcome in healthy men and women","volume":"112","author":"Maor","year":"2013","journal-title":"Am J Cardiol"},{"key":"2026100816023369300_oeag133-B13","doi-asserted-by":"crossref","first-page":"2302","DOI":"10.1161\/CIRCULATIONAHA.112.112300","article-title":"Premature atrial contractions in the general population: frequency and risk factors","volume":"126","author":"Conen","year":"2012","journal-title":"Circulation"},{"key":"2026100816023369300_oeag133-B14","doi-asserted-by":"crossref","first-page":"1904","DOI":"10.1161\/CIRCULATIONAHA.109.874982","article-title":"Excessive supraventricular ectopic activity and increased risk of atrial fibrillation and stroke","volume":"121","author":"Binici","year":"2010","journal-title":"Circulation"},{"key":"2026100816023369300_oeag133-B15","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1001\/jama.2024.22451","article-title":"Atrial fibrillation: a review","volume":"333","author":"Ko","year":"2025","journal-title":"JAMA"},{"key":"2026100816023369300_oeag133-B16","doi-asserted-by":"crossref","first-page":"1453","DOI":"10.1161\/CIRCRESAHA.114.303211","article-title":"The clinical profile and pathophysiology of atrial fibrillation: relationships among clinical features, epidemiology, and mechanisms","volume":"114","author":"Andrade","year":"2014","journal-title":"Circ Res"},{"key":"2026100816023369300_oeag133-B17","doi-asserted-by":"crossref","DOI":"10.1161\/JAHA.118.010078","article-title":"Modifiable predictors of ventricular ectopy in the community","volume":"7","author":"Kerola","year":"2018","journal-title":"J Am Heart Assoc"},{"key":"2026100816023369300_oeag133-B18","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/0002-8703(92)90751-G","article-title":"Determinants of ventricular ectopy in hypertensive cardiac hypertrophy","volume":"123","author":"Schmieder","year":"1992","journal-title":"Am Heart J"},{"key":"2026100816023369300_oeag133-B19","doi-asserted-by":"crossref","first-page":"702","DOI":"10.1136\/heartjnl-2016-309632","article-title":"Risk factors for premature ventricular contractions in young and healthy adults","volume":"103","author":"Von Rotz","year":"2017","journal-title":"Heart"},{"key":"2026100816023369300_oeag133-B20","doi-asserted-by":"crossref","first-page":"985","DOI":"10.1016\/j.jacc.2015.06.488","article-title":"Impact of CARDIOrespiratory FITness on arrhythmia recurrence in obese individuals with atrial fibrillation","volume":"66","author":"Pathak","year":"2015","journal-title":"J Am Coll Cardiol"},{"key":"2026100816023369300_oeag133-B21","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1016\/j.tcm.2025.04.007","article-title":"Premature ventricular complexes and non-sustained ventricular tachycardia in older women","volume":"35","author":"Bohart","year":"2025","journal-title":"Trends Cardiovasc Med"},{"key":"2026100816023369300_oeag133-B22","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1007\/s00424-023-02812-0","article-title":"Age-related increases in cardiac excitability, refractoriness and impulse conduction favor arrhythmogenesis in male rats","volume":"475","author":"Rossi","year":"2023","journal-title":"Pfl\u00fcg Arch"},{"key":"2026100816023369300_oeag133-B23","doi-asserted-by":"crossref","first-page":"2300","DOI":"10.1093\/eurheartj\/ehw053","article-title":"Use of exercise capacity to improve SCORE risk prediction model in asymptomatic adults","volume":"37","author":"Israel","year":"2016","journal-title":"Eur Heart J"},{"key":"2026100816023369300_oeag133-B24","doi-asserted-by":"crossref","first-page":"781","DOI":"10.1056\/NEJMoa022353","article-title":"Frequent ventricular ectopy after exercise as a predictor of death","volume":"348","author":"Frolkis","year":"2003","journal-title":"N Engl J Med"},{"key":"2026100816023369300_oeag133-B25","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1016\/j.hrthm.2022.12.025","article-title":"Cardiopulmonary capacity is reduced in children with ventricular arrhythmia","volume":"20","author":"Pietrzak","year":"2023","journal-title":"Heart Rhythm"},{"key":"2026100816023369300_oeag133-B26","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.80710","article-title":"Cardiac electrophysiological remodeling associated with enhanced arrhythmia susceptibility in a canine model of elite exercise","volume":"12","author":"Poly\u00e1k","year":"2023","journal-title":"eLife"},{"key":"2026100816023369300_oeag133-B27","doi-asserted-by":"crossref","first-page":"1479","DOI":"10.1093\/eurheartj\/ehz897","article-title":"Association between physical activity and risk of incident arrhythmias in 402 406 individuals: evidence from the UK Biobank cohort","volume":"41","author":"Elliott","year":"2020","journal-title":"Eur Heart J"},{"key":"2026100816023369300_oeag133-B28","doi-asserted-by":"crossref","first-page":"e579","DOI":"10.1161\/CIR.0000000000000455","article-title":"Current diagnostic and treatment strategies for specific dilated cardiomyopathies: a scientific statement from the American Heart Association","volume":"134","author":"Bozkurt","year":"2016","journal-title":"Circulation"},{"key":"2026100816023369300_oeag133-B29","doi-asserted-by":"crossref","first-page":"e9","DOI":"10.1161\/CIR.0000000000000682","article-title":"Cardiomyopathy in children: classification and diagnosis: a scientific statement from the American Heart Association","volume":"140","author":"Lipshultz","year":"2019","journal-title":"Circulation"},{"key":"2026100816023369300_oeag133-B30","doi-asserted-by":"crossref","first-page":"2214","DOI":"10.1016\/j.jacc.2024.03.416","article-title":"Arrhythmia-induced cardiomyopathy","volume":"83","author":"Shoureshi","year":"2024","journal-title":"J Am Coll Cardiol"},{"key":"2026100816023369300_oeag133-B31","doi-asserted-by":"crossref","first-page":"2328","DOI":"10.1016\/j.jacc.2019.02.045","article-title":"Arrhythmia-induced cardiomyopathy","volume":"73","author":"Huizar","year":"2019","journal-title":"J Am Coll Cardiol"},{"key":"2026100816023369300_oeag133-B32","doi-asserted-by":"crossref","first-page":"1092","DOI":"10.1161\/CIRCULATIONAHA.105.546432","article-title":"Reversal of cardiomyopathy in patients with repetitive monomorphic ventricular ectopy originating from the right ventricular outflow tract","volume":"112","author":"Yarlagadda","year":"2005","journal-title":"Circulation"},{"key":"2026100816023369300_oeag133-B33","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1161\/01.CIR.0000135472.28234.CC","article-title":"Heart failure and sudden death in patients with tachycardia-induced cardiomyopathy and recurrent tachycardia","volume":"110","author":"Nerheim","year":"2004","journal-title":"Circulation"},{"key":"2026100816023369300_oeag133-B34","doi-asserted-by":"crossref","first-page":"1412","DOI":"10.3390\/jcm12041412","article-title":"Long-term outcomes of tachycardia-induced cardiomyopathy compared with idiopathic dilated cardiomyopathy","volume":"12","author":"Katz","year":"2023","journal-title":"J Clin Med"}],"container-title":["European Heart Journal Open"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/ehjopen\/advance-article-pdf\/doi\/10.1093\/ehjopen\/oeag133\/70825995\/oeag133.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ehjopen\/article-pdf\/6\/5\/oeag133\/70825995\/oeag133.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ehjopen\/article-pdf\/6\/5\/oeag133\/70825995\/oeag133.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T20:02:41Z","timestamp":1791489761000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ehjopen\/article\/doi\/10.1093\/ehjopen\/oeag133\/8772201"}},"subtitle":[],"editor":[{"given":"Frieder","family":"Braunschweig","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2026,8,30]]},"references-count":34,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2026,9,2]]}},"URL":"https:\/\/doi.org\/10.1093\/ehjopen\/oeag133","relation":{},"ISSN":["2752-4191"],"issn-type":[{"value":"2752-4191","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026,9]]},"published":{"date-parts":[[2026,8,30]]},"article-number":"oeag133"}}